Evolution of anti-SARS-CoV-2 immune response in a cohort of French healthcare workers followed for 7 months.

OBJECTIVES: We aimed to understand the immune response among healthcare workers (HCWs) following SARS-CoV-2 infection, and to determine the infection prevalence during the first wave of the pandemic among workers in our hospital. METHODS: Determination of the serological status against SARS-CoV-2 (nucleocapsid) was offered to all HCWs. All HCWs with positive SARS-CoV-2 serology were proposed to be included in a longitudinal medical and serological follow-up (anti-spike) for 7months. RESULTS: We included 3062 HCWs; 256 (8.4%) were positive for anti-SARS-CoV-2 nucleocapsid IgG. Among them, early decrease in the anti-nucleocapsid antibody index was observed between the first (S1) and second (S2) serology samplings in 208 HCWs (84.2%). The initial anti-nucleocapsid IgG index seemed to be related to the HCWs' age. Seventy-four HCWs were included in the 7-month cohort study. Among them, 69 (90.5%) had detectable anti-spike IgG after 7months and 24 (32.4%) reported persistent symptoms consistent with post-acute COVID-19 syndrome diagnosis. CONCLUSION: The prevalence of serological positivity among HCWs was 6.7%. Infection should be followed by vaccination because of antibody decrease.

Infliximab efficacy and safety against refractory systemic necrotising vasculitides: long-term follow-up of 15 patients.

BACKGROUND: Results of uncontrolled studies have suggested that infliximab is efficacious against systemic necrotising vasculitides (SNV) refractory to conventional treatment. However, its safety and ability to induce and maintain remission over the long term remain unknown. OBJECTIVES: To report the use of infliximab to treat refractory SNV, focusing on patients' longer-term outcomes. METHODS: The medical charts of patients given adjunctive infliximab for refractory SNV >/=2 years before this evaluation were reviewed retrospectively. RESULTS: The 15 patients (median age 46 (range 20-69) years, median follow-up 35 (24-41) months) included 10 with Wegener's granulomatosis, 1 microscopic polyangiitis, 3 rheumatoid arthritis-associated and 1 cryoglobulinaemia-related vasculitides. Infliximab was taken for a median time of 8 (2-31) months; 2 patients are still being treated. By day 45, 11 patients had entered remission (Birmingham Vasculitis Activity Score (BVAS) = 0) and 4 others had responded (BVAS decrease >/=50%). Five patients achieved sustained remissions (>/=6 months, corticosteroids

Characterization of the immune response in the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome.

OBJECTIVE: The aetiology of SAPHO (synovitis, acne, palmoplantar pustulosis, hyperostosis, osteitis) syndrome seems to involve genetic, infectious and immunological components. We examined innate and adaptive immune responses in SAPHO syndrome, as compared with PsA and RA. We also studied the effect of etanercept on immunological parameters. METHODS: We studied 29 patients with SAPHO syndrome, as well as 22 patients with RA, 21 patients with PsA and 15 healthy controls. Adaptive immune responses were investigated by assaying total serum immunoglobulins and several autoantibodies. Innate immunity was studied by quantifying blood PMN functions and plasma cytokine levels. PMN responses to Propionibacterium acnes were tested ex vivo. Eight patients who received etanercept for refractory rheumatic disorders were tested before and after 28 days of treatment. RESULTS: SAPHO syndrome was associated with elevated IL-8 and IL-18 plasma levels. IL-8 and TNF-alpha production by purified PMN was higher in the three patient groups than in the healthy controls, but the oxidative burst and IL-18 production were normal. No autoantibodies were detected in SAPHO patients. Induction of PMN IL-8 and TNF-alpha production by P. acnes was impaired in the SAPHO group as compared with the RA and PsA groups. After 28 days of etanercept therapy, PMN IL-8 and TNF-alpha production was down-regulated and TNF-alpha plasma levels were increased. CONCLUSIONS: These results support the view that the SAPHO syndrome may be triggered by an infectious state involving P. acnes, contributing to the strong humoral and cellular pro-inflammatory responses. Etanercept modulation of PMN activation status emphasizes these new immunological findings.

SAPHO syndrome: a long-term follow-up study of 120 cases.

OBJECTIVE: To assess the long-term outcome of the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. METHODS: All patients with the SAPHO syndrome seen at our unit between 1974 and 1997 were identified. Follow-up was prospective from 1992 to 1997. Data before 1992 were analyzed retrospectively. Clinical symptoms, treatments and biological data, including erythrocyte sedimentation rate and C-reactive protein, were recorded at least yearly. When available, radiological data, HLA B27 status, and findings from bone or skin biopsy specimens were recorded. For each drug, an efficacy index (El) was determined as follows: "0" for less than 30% improvement, as judged by the patient, on horizontal visual analog scale, "0.5" for partial efficacy, and "1" for more than 60% improvement. RESULTS: We identified 120 patients with the SAPHO syndrome (50 men, 70 women), of whom 102 patients were followed-up prospectively after 1992; 3 of these 102 patients were lost to follow-up. Six patients also had Crohn's disease, and three had ulcerative colitis. Except for a significant association of palmoplantar pustulosis (PPP) or psoriasis vulgaris (PV) with axial osteitis (P = .007), the dermatologic presentation had no significant influence on rheumatic symptoms (ie, osteitis or arthritis, peripheral or axial). The HLA B27 antigen was not significantly associated with a particular pattern of distribution of arthritis or osteitis. No severe or disabling complications were noted. In the 47 patients followed-up for more than 5 years (mean, 9.5; range, 5 to 23), the mean number of osteitis or arthritis foci increased during follow-up from 1.57 to 1.91 and from 2.68 to 3.11, respectively. Nonsteroidal antiinflammatory drugs (NSAIDs) were prescribed in 113 of 120 (94%) patients, with a mean El of 0.67 (+/-0.39). Corticosteroid (CS) therapy was used in 23 patients, with a mean El of 0.67 (+/-0.42). Colchicine and sulfasalazine had a mean El of 0.36 (+/-0.44) and 0.16 (+/-0.30), in 28 and 18 patients, respectively. Methotrexate was given to 10 patients (6 with peripheral arthritis), with a mean El of 0.64 (+/-0.48). Doxycyclin (100 mg twice daily) was used in 20 patients, usually to treat osteitis, with a mean El of 0.26 (+/-0.42). Intraarticular injections of a CS or osmic acid were used in 27 patients, with a mean El of 0.77 (+/-0.35). CONCLUSIONS: SAPHO syndrome is a relevant and stable entity, with a good long-term prognosis. NSAIDs and intraarticular injections (CS or osmic acid) most often alleviate rheumatic symptoms, but prednisone or methotrexate are sometimes necessary and appear globally helpful.

A reappraisal of quinolone tolerability. The experience of their musculoskeletal adverse effects.

The experience of the rheumatological adverse effects of fluoroquinolones should be helpful for both toxicologists and epidemiologists. In the case of fluoroquinolone-related arthropathy, the paediatric clinical experience seems to support the possible use of newer derivatives like ciprofloxacin in children who really need it. This therapeutic attitude is still contradictory to the labelling of fluoroquinolones. Inversely, there has been an important time-lag between the first reports of fluoroquinolone-related tendinopathies and the official recognition of this unusual toxic phenomenon. This delay, along with the widespread use of fluoroquinolones, makes it difficult to return to more reasonable prescribing guidelines for these very useful and effective anti-microbial compounds. The reasons why potentially serious adverse effects of fluoroquinolones were not anticipated before their commercialisation may be related to the lack of adequate in vitro and in vivo models, and the unexpectedness of the events. When it occurs, fluoroquinolone-induced arthropathy is most frequently benign, and heals without sequelae. The prognosis is not so favourable in the case of fluoroquinolone-related tendinopathy, which carries an important risk of immediate or secondary tendon rupture. Increasingly, fluoroquinolones are being prescribed for benign infections of the urinary or bronchopulmonary tracts. Sometimes, they are even used for antimicrobial prophylaxis before surgical or endoscopic procedures. We believe that for any prescription, the risk/benefit ratio of the fluoroquinolones should be carefully considered, since better tolerated, less expensive drugs can usually be prescribed. Clear information dedicated both to physicians and patients regarding the cautions for use and possible adverse effects of fluoroquinolones would help reduce the risk and severity of adverse reactions. This is especially important for phototoxicity, tendinopathy and cardiovascular adverse effects. As underlined by Ball and Tillotson in this issue, the future clinical use of the fluoroquinolones will be determined by the balance between the antibacterial efficacy and adverse effects of these agents. The adverse reactions affecting the musculoskeletal system provide a good example of this dilemma. Given the absence of an adequate model of tendinopathy and the poor predictivity of animal manifestations in arthropathy and cartilage lesions in humans, careful monitoring of patients during phase II and III trials and, more importantly, long term pharmacovigilance during the postmarketing period, are still strongly warranted.

Lack of correlation between hydrogen peroxide production and nitric oxide production by cultured rabbit articular chondrocytes treated with fluoroquinolone antimicrobial agents.

The arthrotoxicity of fluoroquinolone antibacterial agents so far remains unexplained. Recent experimental data have indicated an early stimulation of the oxidative metabolism within articular chondrocytes. An in vitro model was designed to analyse the production of oxygen-derived reactive species and glutathione by immature rabbit articular chondrocytes, and the influence of different fluoroquinolones on this model was examined. Primary cultures of chondrocytes were exposed to pefloxacin, ofloxacin or ciprofloxacin at 10 mug/ml, for 24 or 48 hr. Flow cytometric analysis used the vital tracer 2',7'-dichlorofluorescein diacetate (DCFH-DA) and evaluated the production of H(2)O(2) and NO by chondrocytes. Separately, NO production and intracellular glutathione levels were evaluated, with the Greiss colorimetric technique and the Tietze method, respectively. With each fluoroquinolone tested, intracellular levels of the fluorescent compound dichlorofluorescein (oxidized form of DCFH-DA) were significantly higher in treated chondrocytes than in control cells. No significant modification of NO or of glutathione cellular levels was noted. Fluoroquinolones stimulate H(2)O(2) production in immature articular chondrocytes, but have no apparent effect on either NO or glutathione production, at least in the early stages of the chondrotoxicity.

Spontaneous spinal epidural hematoma with spinal cord compression complicating plasma cell myeloma. A case report.

STUDY DESIGN: A case is reported in which a patient had acute paraplegia with sensory loss caused by a spontaneous epidural hematoma that was ascribed to bleeding of pre-existing myeloma lesions of the thoracic vertebrae. OBJECTIVES: To highlight the causes of secondary epidural hematomas with special attention to pre-existing vertebral or epidural lesions. SUMMARY OF BACKGROUND DATA: There are no apparent previous reports of epidural spinal hematomas ascribed to underlying malignant diseases. Benign dysplasia, such as hemangioma or Paget's disease, has been implicated in a few cases. METHODS: A case of spontaneous dorsal epidural hematoma is reported in a patient followed up for plasma cell myeloma with osteolytic lesions in the lower thoracic spine. There was no history of major trauma or coagulation disorders. Complete loss of motor and sensory function in both lower limbs was noted, with sphincter dysfunction. Magnetic resonance imaging of the thoracic spine showed a large posterolateral epidural hematoma responsible for spinal cord compression. RESULTS: The patient failed to improve despite surgical decompression within 6 hours of symptom onset. He died 13 days later of refractory bacterial pneumonia. A large epidural hematoma adjacent to myelomatous lesions of the thoracic vertebrae was found at autopsy. CONCLUSIONS: This is the first reported case of spontaneous epidural hematoma ascribed to underlying malignant disease, with confirmation of the diagnosis by postmortem examination. Possible mechanisms include tumor-related epidural inflammation and fragility of epidural venous plexuses.

Tenology: a new frontier.

Tendons were long given little recognition by rheumatologists. Yet, their complex structure and distinctive functional characteristics have been demonstrated by an abundance of histological, biochemical, and biomechanical studies: clearly, tendons are not inert cords linking muscles to bones. The current wave of popularity of sporting activities has brought with it an epidemic of disorders of the tendons, thus focusing attention on these structures. At the same time, modern imaging techniques (particularly magnetic resonance imaging) have allowed clinicians to improve their knowledge of and classification schemes fortendon disorders. Several risk factors, including technical factors, have been identified, so that preventive treatment is now as important as curative treatment. Culture systems for tenocytes (the specialized fibroblasts found in tendons) are now available and have been used to develop experimental models, paving the way for significant advances in tendon repair techniques.

Four cases of tendinopathy in patients on statin therapy.

During the last decade, statins have been widely prescribed as lipid-lowering drugs. Their overall safety profile is good. The main musculoskeletal side effects have consisted of muscle pain and weakness, peripheral neuropathy, and a few cases of drug-induced lupus. We report the first four cases of tendinopathy in patients receiving statin therapy. There were three men and one woman. The diagnoses were extensortenosynovitis at the hands (case 1), tenosynovitis of the tibialis anterior tendon (case 2), and Achilles tendinopathy (cases 3 and 4). Two patients were on simvastatin and two on atorvastatin. The tendinopathy developed 1 to 2 months after treatment initiation. The outcome was consistently favorable within 1 to 2 months after discontinuation of the drug. Similar cases have been reported to French pharmacovigilance centers. This report of four cases of tendinopathy draws attention to a possible and heretofore unrecognized side effect of a drug class that is becoming increasingly popular. Statins are effective in lowering high cholesterol levels in patients with type IIa or IIb hypercholesterolemia. They have been widely used for the last decade, particularly in the secondary and primary prevention of major coronary events. Statins act by inhibiting the enzyme hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Although most patients tolerate statins extremely well, a few experience side effects requiring treatment discontinuation. Reported musculoskeletal side effects include myalgia and a few cases of rhabdomyolysis and polymyositis. Induced lupus and peripheral neuropathy are exceedingly rare.

[Anatomoclinical study of aortic insufficiency in atrophic polychondritis. Apropos of a case]. / Etude anatomo-clinique de l'insuffisance aortique au cours d'une polychondrite atrophiante. A propos d'une observation.

The authors report the anatomo-clinical features of aortic insufficiency complicating atrophic polychondritis, a rare inflammatory disease affecting mainly cartilaginous tissues. This case illustrates the inflammatory changes of the aortic wall, particularly progressive during this disease, responsible for aortic insufficiency and aneurysmal dilatation of the ascending aorta which required aortic valve replacement and prosthetic replacement of the ascending aorta. Histological analysis showed inflammatory lesions of the aortic wall comparable to the cartilaginous lesions described in this condition and suggesting a common physiopathogenic mechanism.

[Sclerosing cholangitis as a complication of Langerhans'cell histiocytosis]. / Cholangite sclérosante compliquant une histiocytose langerhansienne.

INTRODUCTION: Langerhans'cell histiocytosis is a rare and mainly pediatric disease. Patients with hepatic involvement usually have a disseminated form of the disease, with poor prognosis. Sclerosing cholangitis can occur in 10 to 15% of multivisceral Langerhans'cell histiocytosis. We report the case of a 56-years-old patient who developed sclerosing cholangitis 12 years after the diagnosis of Langerhans'cell histiocytosis. EXEGESIS: A 56-years-old man was admitted because of rapid general health impairment with epigastric pain. He was diagnosed as having Langerhans'cell histiocytosis 12 years ago because of a diabetes insipidus. Lungs were involved and during follow-up vertebral osteocondensation also developed. However, Langerhans'cell histiocytosis was clinically silent at the time of admission, without any treatment. Biologically, cholestasis and inflammation were noted. Digestive radiological investigations (echo-endoscopy, CT-scan, MRI) showed homogenous hepatomegaly and a diffuse infiltration of intra and extrahepatic bile ducts. Liver biopsy yielded the diagnosis of sclerosing cholangitis. Clinical and biological improvement occurred with oral corticosteroids (at 12 months after sclerosing cholangitis diagnosis). CONCLUSION: Sclerosing cholangitis is a potential complication of Langerhans'cell histiocytosis, mainly in its multivisceral form. It can occur at a median of 2 years after diagnosis in children, but occasionally much later in adults, whereas Langerhans'cell histiocytosis seems quiescent. Diagnosis is supported by radiological investigations and liver biopsy. As no drug therapy appears clearly effective, liver transplantation must frequently be considered in these patients.

[Fatal infectious complications in 2 patients with adult onset Still disease]. / Complications infectieuses fatales chez deux patients atteints de maladie de Still de l'adulte.

If adult Still's disease (ASD) can sometimes lead to severe destructive joint lesions and to various systemic manifestations, life-threatening complications are very rare. However, a long-term and high-dose corticosteroid therapy is often required to control the disease, with frequent corticodependence. Some authors have proposed methotrexate as a second line drug for ASD, that could permit a corticosteroid sparing effect. We report two cases of acute fatal infectious complications--legionella pneumonitis and multiple brain abscess caused by Nocardia asteroides--in two patients treated for ASD with both corticosteroids and methotrexate. These two cases raise the problem of the immunodepression induced by this combination therapy and point out the difficulties in aggressive forms of ASD.

[A case of post-partum remission of acquired dyserythropoiesis, a rare cause of anemia in disseminated lupus erythematosus]. / Une observation de rémission post-partum d'une dysérythropoïèse acquise, une cause rare d'anémie au cours du lupus érythémateux disséminé.

INTRODUCTION: Amongst the various causes of anemia in systemic lupus erythematosus, isolated and acquired erythrocyte dysplasia is rare and most often part of global dysmyelopoiesis. EXEGESIS: The authors report a case of acquired erythrocyte dysplastic syndrome that occurred in a 34-year-old woman in whom previous diagnosis had evidenced systemic lupus erythematosus of rather benign course. Other causes of dysmyelopoiesis were ruled out. Myeloid stem cell cultures showed selective inhibition of erythroid cells growing, with no particular effect of the patient's serum. While a corticosteroid treatment with prednisone (1 mg/kg/d) did not show any efficacy upon anemia, the patient's pregnancy was followed by prolonged correction of hemoglobin, making possible the tapering of prednisone down to 10 mg/d. CONCLUSION: Acquired erythrocyte dysplastic syndrome remains a rare cause of anemia in systemic lupus erythematosus. This case report suggests an immunological phenomenon, but the mechanisms underlying both the appearance and long-lasting remission after pregnancy remain unexplained.

[Primary carpal bone defect]. / Géodes dites primitives du carpe.

We present a review of management options in case of carpal bone defect, a relatively frequent discovery. In the literature, diagnosis is usually a fortuitous radiographic finding showing one or several images of carpal defect. Pain is observed in some cases, more exceptionally pathological fracture. The scaphoid, lunatum and hamatum are most frequently involved. Bilateral defects may be observed. Different mechanisms have been put forward to explain the development of intraosseous defects in the carpal bones including intraosseous penetration of synovial tissue, or in situ metaplasia of bone tissue. The main differential diagnoses are osteonecrosis sequellae (for the lunatum and the scaphoid), subchondral defects due to hyperpression and arthropathies in dialysis patients. All authors propose simple surveillance for asymptomatic images. In case of pain, with soft tissue swelling or pathological fractures, filling-excision is warranted depending on the severity of the clinical signs. Prognosis is generally good and recurrence exceptional.

[Involvement of the hip in systemic-onset forms of juvenile chronic arthritis. Retrospective study of 28 cases]. / L'atteinte de la hanche au cours des formes à début systémique d'arthrite chronique juvénile. Etude rétrospective de 28 cas.

The objective of this work was to evaluate the course of hip disease in patients with systemic-onset juvenile chronic arthritis. 59 patients with systemic-onset juvenile chronic arthritis followed-up for a mean of 15 years (+/- 6 years) were studied retrospectively. 28 patients (47.5%) had involvement of the hip. Mean age at onset of symptoms of hip disease was 9.5 years (+/- 5 years). Hip arthritis was always preceded by other manifestations of the disease, including arthritis of other lower limb joints. Mean time interval between onset of the disease and onset of hip symptoms was 6.3 years (+/- 3 years). In 66% of cases, symptoms occurred simultaneously in both hips. Eight of nine patients with initially unilateral hip arthritis subsequently developed arthritis of the other hip; in four patients, less than one year elapsed between involvement of the two hips. Roentgenographic changes were variable and included acetabular protrusion (25%), complex cervico-cephalic and acetabular growth disorders (21%), subdislocation (18%), a short femoral neck with varus deformity (14%), and a long femoral neck with valgus deformity (14%). Avascular necrosis of the femoral head occurred in three patients. Roentgenographic evidence of repair was seen in one patient. Among the ten patients who required surgery, two had corrective osteotomy with adductor tenotomy and eight had total hip arthroplasty (of both hips in six patients) with good short- and medium-term outcomes. After arthroplasty, a single patient required reoperation in the short term, for persistent flexion contracture. Loosening of the acetabular arthroplasty required revision in two patients 5 and 10 years, respectively, after the initial procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

European League Against Rheumatism Sjögren's Syndrome Disease Activity Index and European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index: a complete picture of primary Sjögren's syndrome patients.

OBJECTIVE: The European League Against Rheumatism (EULAR) Sjögren's Syndrome (SS) Disease Activity Index (ESSDAI) and the EULAR SS Patient-Reported Index (ESSPRI) were recently developed. We aimed to determine whether patients' symptoms differed between patients with and without systemic involvement and if the disease-specific indices correlated with each other in primary SS. METHODS: Fifteen French centers included 395 primary SS patients in the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome Cohort. At enrollment, physicians completed the ESSDAI, the SS Disease Activity Index (SSDAI), and the Sjögren's Systemic Clinical Activity Index (SCAI), and patients completed the ESSPRI, the Sicca Symptoms Inventory, and the Profile of Fatigue and Discomfort. All scores were compared between patients with and without systemic involvement. Correlations between scores of systemic activity and patients' symptoms were obtained. RESULTS: At enrollment, 120 (30.4%) patients had never experienced systemic complication and 155 (39.2%) patients and 120 (30.4%) patients had, respectively, only past or current systemic manifestations. Past or current systemic patients had higher levels of symptoms, except dryness. The ESSDAI did not correlate with the patient-scored ESSPRI (rho = 0.06, P = 0.30), whereas the SSDAI and the SCAI, which include subjective items, did correlate (rho = 0.28 and 0.25, respectively; P < 0.0001 for both). CONCLUSION: Alterations of common patient-reported outcomes are present in all patients with primary SS, including those with systemic complications. However, patient symptoms and systemic complications are 2 different facets of primary SS. Therefore, the use of both systemic and patients' indices, such as the ESSDAI and ESSPRI, are useful. Since these 2 facets weakly overlap, one should identify which of both components is the main target of the treatment to test, when designing clinical trials in primary SS.